Modern organic chemists have as one goal the development of new synthetic routes for the controlled, efficient production of asymmetric compounds. Saturated carbon atoms, constituting the backbones of most organic compounds, are attached to adjacent atoms through a tetrahedral arrangement of chemical bonds. If the four bonds are to different atoms or groups, the central carbon provides a chiral, or asymmetric, center and the compound therefore may have the ability to exist in two mirror image, or enantiomeric, forms. It is crucial when synthetic organic chemists attempt to prepare these asymmetric compounds to have a means to produce the desired enantiomer because compounds of the wrong enantiomeric form often lack desirable biological, physical or chemical properties.
A particularly attractive approach to the synthesis of optically active compounds is the catalytic asymmetric generation of carbon-carbon bonds. This approach is highly efficient because the optical activity is installed during the assembly of the carbon skeleton rather than as a separate, subsequent operation. Among such reactions the enantioselective addition of organometallic reagents to aldehydes has received much attention in the literature. This transformation represents the enantioselective version of the venerable Grignard addition and affords broadly useful, optically active secondary alcohols as products. Organozinc reagents are usually employed as the organometallic reactant since they do not react with aldehydes in the absence of a catalyst.
General reviews cite the use of optically active .beta.-aminoalcohols to catalyze the asymmetric addition of organozinc reagents to aldehydes (Noyori, R., Kitamura, M., Angew. Chem., Int. Ed. Engl. 1991, 30,49; Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833). Among such catalysts, the best known and most widely used appears to be 3-exo-(dimethylamino)isoborneol, more commonly known as DAIB (Kitamura, M. et al., J. Am. Chem. Soc. 1986, 108, 6071). DAIB allows highly selective addition of organozinc reagents to certain aldehydes, especially aryl derivatives. However, DAIB requires an expensive and complex 6-step synthesis and is not suitable for addition of organozinc reagents to sterically encumbered aldehydes such as pivalaldehyde. Other aminoalcohols such as N,N-dibutylnorephedrine or DBNE (Soai, K. et al., J. Org. Chem. 1991, 56, 4264) are easier to prepare but are less selective catalysts than DAIB.
Clearly, a need exists for an improved catalyst for the asymmetric addition of organozinc reagents to aldehydes which is both readily synthesized and provides high selectivity with a wide range of aldehyde substrates. The present invention provides an improved process for the synthesis of compounds in a desired enantiomeric form. Other objects and advantages of the invention will become apparent to those skilled in the art upon reference to the detailed description, which hereinafter follows.